Genome-Wide Association Scan of Serum Urea in European Populations Identifies Two Novel Loci

Am J Nephrol. 2019;49(3):193-202. doi: 10.1159/000496930. Epub 2019 Feb 26.

Abstract

Background: Serum urea level is a heritable trait, commonly used as a diagnostic marker for kidney function. Genome-wide association studies (GWAS) in East-Asian populations identified a number of genetic loci related to serum urea, however there is a paucity of data for European populations.

Methods: We performed a two-stage meta-analysis of GWASs on serum urea in 13,312 participants, with independent replication in 7,379 participants of European ancestry.

Results: We identified 6 genome-wide significant single nucleotide polymorphisms (SNPs) in or near 6 loci, of which 2 were novel (POU2AF1 and ADAMTS9-AS2). Replication of East-Asian and Scottish data provided evidence for an additional 8 loci. SNPs tag regions previously associated with anthropometric traits, serum magnesium, and urinary albumin-to-creatinine ratio, as well as expression quantitative trait loci for genes preferentially expressed in kidney and gastro-intestinal tissues.

Conclusions: Our findings provide insights into the genetic underpinnings of urea metabolism, with potential relevance to kidney function.

Keywords: Genome-wide association studies; Kidney function; Serum urea.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology
  • Genome-Wide Association Study
  • Humans
  • Kidney / metabolism*
  • Metabolic Networks and Pathways / genetics
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • Reference Values
  • Urea / blood*
  • Urea / metabolism
  • White People / genetics*

Substances

  • Urea